Injection Of Diphenhydramine Research Articles

Biphasic anaphylaxis reaction in adult female: how to approach?

Anaphylaxis is a severe allergic reaction, usually occurring one to two hours after exposure to an allergen, that can lead to death. Estimated lifetime prevalence of anaphylaxis is 1.6-5.1%, with global incidence between 50 to 112 episodes per 100.000 persons per year. Biphasic anaphylaxis is a form of recurrent anaphylaxis occurring between 1 to 72 hours after resolution of initial anaphylactic episode. Our case presents an 18-year-old female patient admitted to the emergency department (ED) with chief complaint of shortness of breath and swollen eyes after contact with caterpillar while gardening. General physical examination presented tachycardia, tachypnea, angioedema, urticaria. Localized lung examination presented bilateral wheezing. Patient fulfilled NIAID/FAAN criteria. Patient was administered 0.3 mg epinephrine intramuscular, diphenhydramine injection 10 mg, dexamethasone injection 5 mg, and observed in ED for 1 hour. Patient was then transferred to intensive care unit (ICU) and was in resolution. However, patient presented again with initial symptoms of dyspnea, swollen eyes, and itchiness while under observation. The objective of this paper is to present a rare case of biphasic anaphylaxis and further highlight the importance of awareness to occurrence of biphasic anaphylaxis.

Safety and technical success of diphenhydramine as an alternative local anaesthetic agent for radiology procedures

To evaluate retrospectively the safety and technical success of subcutaneous diphenhydramine as an alternative local anaesthetic for radiology procedures. Between January 2000 and April 2021, 84 image-guided procedures were performed in 81 adult patients (mean age 61 years, 86% female) using 1% injectable diphenhydramine as a local anaesthetic. Indications were history of severe allergy to "-caine" local anaesthetics in 76 (90%) patients and recent administration of bupivacaine liposomal injectable suspension in eight (10%) patients. Twelve of the 84 (14%) procedures were performed with concomitant moderate sedation. Patient characteristics, procedural techniques, and clinical outcomes were reviewed. Early and delayed (30-day) complications were classified as either related to local diphenhydramine injection or to the procedure itself. Procedure-related complications were gradated using the Clavien-Dindo system. Percutaneous biopsy was the most frequently performed procedure (57/84, 67%). Fifty-nine (70%) of the 84 procedures were ultrasound guided. The most common procedural site was the breast (34/84, 40%). All procedures were technically successful. There were two minor injection-related complications related to post-procedural pain. A single minor procedure-related complication involved a patient requiring hospital admission for post-renal biopsy related haematuria. Injectable diphenhydramine appears to be a safe and effective local anaesthetic alternative in patients with "-caine" class contraindications undergoing radiology procedures. A future prospective trial would be useful to assess the safety profile in an large cohort of patients.

The Effect of Intraoperative Diphenhydramine/Morphine on Acute Pain and Opioid Consumption after Spine Surgery

Background: One of the most common problems after spine surgery is very severe pain that usually affects outcome of patients after surgery and duration of hospital stay. Acute postoperative pain has several mechanisms, and multimodal analgesia by different mechanism of action will help control to it. In this study, we intended to investigate the effect of intravenous diphenhydramine injection during induction of anesthesia and morphine before incision on the control of acute pain in postoperative laminectomy. Methods: 130 patients scheduled for spine surgeries were assigned to receive a single pre induction dose of diphenhydramine 0.4mg/kg IV (D group) and morphine 0.15mg/kg before incision in addition acetaminophen 1gr IV at the end of surgery and just morphine 0.15mg/kg and acetaminophen 1gr IV (C group) in a randomized, double-blind trial. Postoperative pain, analgesic requirements in recovery and 24 hr after surgery were assessed. Results: The mean pain intensity in recovery was lower in the diphenhydramine group than in the control group (MD, 2.13; 95% confidence interval (CI), 1.72–2.53; P < .0001) and the need for analgesia was much lower in the diphenhydramine group than in the control group. P < 0.001. The severity of pain and the need for analgesics in the diphenhydramine group had a significant decrease in the ward compared to the control group. Conclusion: Prophylactic diphenhydramine 0.4 mg/kg at induction of general anesthesia in combination with morphine 0.15mg/kg before incision and acetaminophen 1gr at the end of surgery reduced the postoperative severity of acute pain and opioids requirement in the early postoperative period after spine surgeries.

Mannitol Enhances the Antinociceptive Effects of Diphenhydramine as an Alternative Local Anesthetic.

Mannitol has recently been reported to be effective in enhancing the antinociceptive efficacy of lidocaine. No single study to date, however, has compared diphenhydramine with and without mannitol for nociceptive processing as an alternative local anesthetic. In this study, we examined the antinociceptive efficacy enhancements of diphenhydramine when combined with mannitol. Male Sprague-Dawley rats weighing 230–260 g were used in a hot plate test to evaluate the antinociceptive effects of diphenhydramine. All chemicals were dissolved in isotonic normal saline and administered subcutaneously into the plantar surface of the right hind paw at 10 min before the hot plate test. A subcutaneous injection of 0.5% or 1% diphenhydramine produced significant inhibition of the withdrawal latency time compared with the vehicle treatment. Antinociceptive effects appeared 10 min after the diphenhydramine injections and persisted for over 30 min. The antinociceptive effects of 1% diphenhydramine were not statistically different from those of 1% lidocaine. Although a subcutaneous injection of a 0.5 M mannitol solution alone did not affect the withdrawal latency time, 1% diphenhydramine with 0.5 M mannitol significantly enhanced antinociception. A subcutaneous injection of 1% diphenhydramine with epinephrine (1 : 100,000) solution did not increase the antinociceptive effect of the diphenhydramine. These results suggest that diphenhydramine with mannitol can be used as an alternative local anesthetic.

A qualitative study of diphenhydramine injection in Kyrgyz prisons and implications for harm reduction

BackgroundTo reduce opioid dependence and HIV transmission, Kyrgyzstan has introduced methadone maintenance therapy and needle/syringe programs into prisons. Illicit injection of diphenhydramine, an antihistamine branded as Dimedrol®, has been anecdotally reported as a potential challenge to harm reduction efforts in prisons but has not been studied systematically.MethodsWe conducted qualitative interviews in Kyrgyz or Russian with prisoners (n = 49), former prisoners (n = 19), and stakeholders (n = 18), including prison administrators and prisoner advocates near Bishkek, Kyrgyzstan from October 2016 to September 2018. Interviews explored social–contextual factors influencing methadone utilization in prisons. Transcripts were coded by five researchers using content analysis. Dimedrol injection emerged as an important topic, prompting a dedicated analysis.ResultsAfter drinking methadone, some people in prison inject crushed Dimedrol tablets, a non-prescription antihistamine that is banned but obtainable in prison, to achieve a state of euphoria. From the perspectives of the study participants, Dimedrol injection was associated with devastating physical and mental health consequences, including psychosis and skin infections. Moreover, the visible wounds of Dimedrol injecting contributed to the perception of methadone as a harmful drug and supporting preference for heroin over methadone.ConclusionDimedrol injecting is a potentially serious threat to harm reduction and HIV prevention efforts in Kyrgyzstan and elsewhere in the Eastern European and Central Asian region and requires further investigation.

310 IV Cetirizine Versus IV Diphenhydramine in Treatment of Acute Urticaria

Acute urticaria, the most common symptom of acute allergic reactions, is a frequent presentation in the emergency department (ED). Diphenhydramine injection, the only available antihistamine injection, is sedating, short in duration with anticholinergic side effects. Cetirizine injection 10 mg/mL, a recent innovation in antihistamine pharmacology, may minimize these problems. A multicenter phase III randomized trial was conducted, in which a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Adult subjects who presented to 19 EDs and urgent care centers (UCCs) with acute urticaria requiring IV antihistamine injections were randomized to either IV cetirizine 10 mg or IV diphenhydramine 50 mg. Primary endpoint was the 2-h pruritus score change from baseline, using a previously validated scoring scale. Key secondary endpoints were time spent in treatment center and need to return to ED/clinic. Patient sedation was scored at 1 h, 2 h, and discharge. Other secondary endpoints (rescue drugs, symptom recurrence, etc) were also measured. Adult subjects (n=262) were enrolled from March 2017 to April 2018. The 2-hour pruritus score change from baseline from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine (change from baseline in diphenhydramine group, -1.50 (SD 0.984); change from baseline in cetirizine group, -1.61 (SD 0.944); p=NS). Time spent in treatment center was 2.1 h in the diphenhydramine group vs 1.7 h in the cetirizine group (p=0.0024). Return to ED/Clinic was 14.0% in the diphenhydramine group and 5.5% in the cetirizine group (p=0.0232). There was significantly less sedation in the cetirizine group at 1h (p=0.0034), 2 h (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. There were significantly fewer adverse events (p=0.0083) and fewer rescue drug usages (p=0.0159) reported in subjects treated with cetirizine compared to diphenhydramine. This study demonstrates IV cetirizine as an effective alternative to IV diphenhydramine in the treatment of acute urticaria with less sedation, fewer adverse events, less symptom recurrence, less rescue drug use, shorter time to discharge and lower readmission to EDs and UCCs.

INTRAVENOUS (IV) CETIRIZINE SHOWS GREATER OVERALL BENEFIT TO IV DIPHENHYDRAMINE FOR ACUTE URTICARIA

Introduction Acute urticaria is the most common symptom of acute allergic reactions. Diphenhydramine injection, the only available H1-antihistamine injection, is a 1stgeneration antihistamine with many side effects including sedation, short duration, anticholinergic effect, drug-drug interactions. Cetirizine injection, the first innovation in the H1-antihistamine injection space since 1955, minimizes these problems. A phase 3 clinical trial using a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Methods 262 adult patients with acute urticaria and in need of IV H1-antihistamine injections were randomized to either IV cetirizine or IV diphenhydramine. Primary efficacy was the “2-hour pruritus score change from baseline”. Key secondary endpoints were “time spent in treatment center” and “need to return to ED/clinic within 48 hours”. Patient sedation was scored at 1 hour, 2 hours, and discharge. Results The “2-hour pruritus score change from baseline” from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine, and in favor of cetirizine. “Time spent in treatment center” was 2.07 hours in the diphenhydramine group and 1.71 hours in cetirizine (per protocol p=0.0024). “Return to ED/Clinic” was 14% in the diphenhydramine group and 5.5% in cetirizine (p=0.0232). Data also showed significantly less sedation in the cetirizine group at 1hr (p=0.0034), 2hr (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. Conclusions IV cetirizine is an effective alternative to IV diphenhydramine in the treatment of acute urticaria with benefits of less sedation, less AE, earlier discharge, less symptom recurrence, and less return to treatment center.

Safe Use of Subcutaneous Diphenhydramine in the Inpatient Hospice Unit.

Diphenhydramine (DPH) is most commonly used via oral, topical, intramuscular (IM) and intravenous (IV) routes for the palliation of pruritus, treatment of extrapyramidal symptoms, management of parkinsonism and for allergic reactions. However, many hospice patients are unable to take oral medications and/or do not have IV access. Moreover, topical administration has a relatively slow rate of absorption. For this reason, in the hospice setting it is not uncommon for diphenhydramine to be administered via the subcutaneous (SC) route secondary to its ease of access, low infection rates and its low levels of discomfort. In contrast, outside the hospice setting, subcutaneous DPH has not been widely used, primarily because of a handful of case reports published in the 1990's that report skin necrosis following subcutaneous administration of DPH for local anesthesia. Since these early case reports, however, there has been very little in the way of research to examine this further. The aim of this study is to provide objective data concerning the safe use of subcutaneous diphenhydramine, as part of our efforts to improve upon safe practices in our organization. This is a retrospective review of records from 6 of our inpatient hospice units obtained from our pharmacy database for patients who received at least one subcutaneous injection of diphenhydramine between 2012-2015. Selected patients were then subsequently screened for post-administration skin necrosis, as recorded in our quality assurance database during the same time period. A total of 648 diphenhydramine subcutaneous injections were administered in109 individual patients. None of the patients were reported to have an adverse cutaneous reaction. This retrospective review demonstrates that subcutaneous diphenhydramine injection is a safe alternative to oral and other parenteral routes, and may be particularly valuable in terminally ill patients, who are often unable to swallow and are without IV access.

Diphenhydramine dependence through deep intramuscular injection resulting in myonecrosis and prolonged QT interval

Diphenhydramine (DPH) is a first-generation antihistamine, which is useful in treating allergic reaction, and is usually considered innocuous. We describe a retired nurse with history of depression, who began to develop drug-seeking behaviour after her first receiving of an intramuscular (IM) DPH injection due to urticaria. The 49-year-old patient had developed IM DPH dependence within 4 months. She needed to receive psychiatric inpatient treatment because of depressive mood, serious myonecrosis over injected sites, and prolongation of QT interval. This is the first reported case of DPH dependence through the IM route. Second-generation antihistamines might be better choices for patients with psychiatric illness by reason of their lower effects on central nervous system and lower risk of abuse.

A role for histamine in cardiovascular regulation in late stage embryos of the red-footed tortoise, Chelonoidis carbonaria Spix, 1824

A chorioallantoic membrane artery in embryos of the red-footed tortoise, Chelonoidis carbonaria was occlusively cannulated for measurement of blood pressure and injection of drugs. Two age groups of embryos in the final 10% of incubation were categorized by the ratio of embryonic body to yolk mass. All embryos first received cholinergic and β-adrenergic blockade. This revealed that β-adrenergic control was established in both groups whereas cholinergic control was only established in the older group immediately prior to hatching. The study then progressed as two series. Series one was conducted in a subset of embryos treated with histamine before or after injection of ranitidine, the antagonist of H2 receptors. Injection of histamine caused an initial phasic hypertension which recovered, followed by a longer lasting hypertensive response accompanied by a tachycardia. Injection of the H2 receptor antagonist ranitidine itself caused a hypotensive tachycardia with subsequent recovery of heart rate. Ranitidine also abolished the cardiac effects of histamine injection while leaving the initial hypertensive response intact. In series, two embryos were injected with histamine after injection of diphenhydramine, the antagonist to H1 receptors. This abolished the whole of the pressor response to histamine injection but left the tachycardic response intact. These data indicate that histamine acts as a non-adrenergic, non-cholinergic factor, regulating the cardiovascular system of developing reptilian embryos and that its overall effects are mediated via both H1 and H2 receptor types.

First and second generation H1 histamine receptor antagonists produce different sleep-inducing profiles in rats

First generation H1 histamine receptor antagonists, such as d-chlorpheniramine (d-CPA) and diphenhydramine, produce drowsiness in humans. They are currently used as over-the-counter sleep aids. However, the mechanisms underlying drowsiness induced by these H1 histamine receptor antagonists remain obscure because they produce heterogeneous receptor-independent actions. Ketotifen is a second generation H1 histamine receptor antagonist which is more permeable to the brain than newer H1 histamine receptor antagonists. Therefore, to access sleep-inducing profiles by H1 histamine receptor blocking actions, the present study compared the dose-dependent effects of diphenhydramine and ketotifen (1–40mg/kg, intraperitoneal injection at dark onset time) on daily sleep–wake patterns in rats. Ketotifen dose-dependently decreased rapid-eye-movement (REM) sleep and increased non-REM sleep by amplifying slow-wave electroencephalogram powers. Diphenhydramine at 4mg/kg transiently increased non-REM sleep and reduced REM sleep similar to the effects of ketotifen. The larger injections of diphenhydramine (10–40mg/kg), however, reduced non-REM sleep, abolished slow-wave enhancements and facilitated wakefulness. The bi-directional action of diphenhydramine on sleep is similar to our former results using d-CPA. Taken together, the arousal effects caused by over-dose administrations of the first generation H1 histamine receptor antagonists may be mediated by H1 histamine receptor-independent actions. To further examine the tolerance of ketotifen-induced sleep, 3mg/kg ketotifen was injected daily for 5days 3h before light onset time. These experiments consistently enhanced non-REM-sleep at the end of the active phase of rats, suggesting that ketotifen may function as a desirable sleep aid although the coincidental REM sleep reduction requires attention.

Effect of histamine on regional cerebral blood flow of the parietal lobe in rats

Histamine is a powerful modulator that regulates blood vessels and blood flow. The effect of histamine on the extracortical vessels has been well described, while much less is known about the effect of histamine on intracortical vessels. In this study, we investigated the effect of histamine on regional cerebral blood flow in rat parietal lobe with laser Doppler flowmetry. The pharmacological characteristics of distinct ways (intracerebroventricular injection, intraperitoneal injection, and cranial window infusion) in applying histamine to the brain were also obtained and compared. Histamine applied in three ways all produced a decrease of rCBF in parietal lobe in a concentration-dependent manner. Cranial window infusion was the most effective way and intraperitoneal injection of L-histidine was the most ineffective, although it is a simple and applied way. To determine which type of receptor takes part in the vessel contraction induced by histamine, H1 receptor antagonist, diphenhydramine, and H2 receptor antagonist, cimetidine, were applied, respectively, before histamine administration. When the injection of cimetidine was conducted in advance, histamine still resulted in a decrease of infusion amount; while the injection of diphenhydramine was conducted in advance, the infusion of blood amount wasn't changed. These findings indicated that histamine could result in a reduction of rCBF in the rat parietal lobe and this effect of histamine may attribute partly to its combination with H1 receptor.

Effects of Anserine on the Renal Sympathetic Nerve Activity and Blood Pressure in Urethane-Anesthetized Rats

Previous studies have demonstrated that central injection of L-carnosine (beta-alynyl-L-histidine), dipeptide synthesized in mammalian muscles, affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in anesthetized rats. In the present study, using urethane-anesthetized rats, we examined the dose-dependent effects of intravenous (IV) injection of various doses of anserine, dipeptide of similar structure to L-carnosine, on RSNA, BP and heart rate (HR). We found that injection of a low dose of anserine (1 microg) significantly suppressed RSNA, BP and HR. Conversely, a high dose (1000 microg) of anserine significantly elevated RSNA, BP and HR. Pretreatment with lateral cerebral ventricular (LCV) injection of thioperamide, a histaminergic H(3)-receptor antagonist, eliminated the effects of a low dose of anserine on RSNA, BP and HR. LCV injection of diphenhydramine, a histaminergic H(1)-receptor antagonist, abolished the effects of a high dose of anserine on RSNA, BP and HR. These findings suggest that anserine affects RSNA, BP and HR in a dose-dependent manner, and that the histaminergic nerve may be involved in the dose-different effects of anserine in rats.

Comparison of diphenhydramine and lidocaine for prevention of pain after injection of propofol

Pain on injection is still a problem with propofol. The purpose of the study was to compare the effectiveness of diphenhydramine and lidocaine on pain caused by propofol at the site of injection. One hundred and eighty ASA I-II adults undergoing elective surgery were randomly assigned into three groups of 60 each. Group I (placebo) received 2 mL normal saline, Group II received 2 mL (40 mg) 2% lidocaine and Group III received 2 mL (20 mg) diphenhydramine intravenously (i.v.) during a 1-min venous occlusion, followed by propofol into a cephalic forearm vein of the antecubital fossa. Pain assessment was made immediately after propofol injection. In the placebo group 25 (41.7%) patients experienced pain during propofol injection as compared to 2 (3.3%) and 3 (5.0%) in the lidocaine and diphenhydramine groups, respectively. The prevalence of pain and pain score were significantly less in both the lidocaine and diphenhydramine groups than in the placebo group (P = 0.00). No difference was found between the diphenhydramine and lidocaine groups (P = 0.60). Previous injection of diphenhydramine with venous occlusion can be considered as an alternative to lidocaine for reducing the prevalence of pain caused by injection of propofol into peripheral veins.

Dose-Different Effects of Orexin-A on the Renal Sympathetic Nerve and Blood Pressure in Urethane-Anesthetized Rats

Previous studies have demonstrated that central injection of orexin-A affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in both anesthetized and unanesthetized rats. In the present study, we examined, using urethane-anesthetized rats, the dose-dependent effects of intravenous (iv) or intralateral cerebral ventricular (LCV) injection of various doses of orexin-A on RSNA and BP. We found that injection of a low dose of orexin-A (10 ng iv or 0.01 ng LCV) suppressed RSNA and BP significantly. Conversely, a high dose (1000 ng iv or 10 ng LCV) of orexin-A elevated both RSNA and BP significantly. Pretreatment with either iv or LCV injection of thioperamide, a histaminergic H(3)-receptor antagonist, eliminated the effects of a low dose of orexin-A on both RSNA and BP. Both iv and LCV injection of diphenhydramine, a histaminergic H(1)-receptor antagonist, abolished the effects of a high dose of orexin-A on RSNA and BP. Furthermore, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of both low and high doses of orexin-A on RSNA and BP. These findings suggest that orexin-A affects RSNA and BP in a dose-dependent manner and that the SCN and histaminergic nerve may be involved in the dose-different effects of orexin-A in rats.

USE OF HYPOSENSITIZATION INJECTIONS TO CONTROL SEASONAL PRURITUS IN A BACTRIAN CAMEL (CAMELUS BACTRIANUS)

A 9-yr-old, female Bactrian camel (Camelus bactrianus) developed severe pruritus in June 1993. During the next 8 yr, the camel exhibited annual episodes of pruritus and epiphora, generally beginning in June and subsiding in October of each year. These signs could usually be controlled with topical agents and fly repellents, although pruritus flare-ups were effectively controlled with intermittent injections of diphenhydramine and corticosteroids. There were no signs during the colder months. The pruritus became more severe and difficult to control when the camel reached its 18th year. Histopathologic descriptions of skin biopsies taken from several sites suggested a hypersensitivity reaction with secondary changes because of bacterial infection or corticosteroid administration (or both). An intradermal test (IDT) performed using 62 allergens regionalized to Northern California resulted in 17 positive test sites. Hyposensitization therapy was initiated using allergens chosen on the basis of exposure, availability, and the results of the IDT, using standard protocols. The clinical signs of pruritus were markedly reduced in the 2 yr after the hyposensitization injections were initiated.

Olfactory stimulation with scent of grapefruit oil affects autonomic nerves, lipolysis and appetite in rats

In a previous study, we found that olfactory stimulation with scent of grapefruit oil (SGFO) excites the sympathetic nerve innervating the white adipose tissue in rats. Here we further examined the effects of SGFO in rats and observed that olfactory stimulation with SGFO excited the sympathetic nerves innervating the brown adipose tissue and adrenal gland and inhibited the parasympathetic gastric nerve. Local anesthesia of the nasal mucosa with xylocaine or anosmic treatment using ZnSO 4 eliminated the autonomic changes caused by SGFO. Moreover, stimulation with SGFO elevated the plasma glycerol level, and treatment with either ZnSO 4 or an intraperitoneal injection of diphenhydramine, a histamine H1 receptor-antagonist, abolished the glycerol elevation by SGFO. Furthermore, a 15-min exposure to SGFO three times a week reduced food intake and body weight. Finally, limonene, a component of grapefruit oil, induced reponses similar to those caused by SGFO, and diphenhydramine eliminated the glycerol response to limonene. Thus, the scent of grapefruit oil, and particularly its primary component limonene, affects autonomic nerves, enhances lipolysis through a histaminergic response, and reduces appetite and body weight.

Role of histaminergic neurons in development of epileptic seizures in EL mice

The EL mouse is an animal model for hereditary temporal lobe epilepsy. When the mice receive weekly vestibular stimulation, e.g., 30 “tosses”, 10–15 cm vertically, they start to convulse after 1–2 weeks. The aim of this study was to evaluate the role of the histaminergic neurons in the regulation of seizure development in the EL mice. The obtained results indicated that administration of either histidine, a substrate for histamine synthesis, or metoprine (2,4-diamino-5-(3,4-dichlorophnyl)-6-methyl-pyrimidine), an inhibitor of histamine N-methyltransferase (HNMT), retarded the onset of seizure episodes in the mice. The co-administration of histidine and metoprine caused a more marked delay in it. The histamine levels in the brain significantly increased in response to any of these treatments. The intraperitoneal injection of diphenhydramine, a H1-antagonist accelerated the initiation of seizure episodes in the mice, whereas thioperamide, a H3-antagonist caused a delay in the response. There were significant increases in the brain histamine levels upon injection of any of these drugs with concomitant rises in the activity of the histidine decarboxylase (HDC). These results, taken together, suggest that the histaminergic neurons play crucial roles in the development of seizures in the EL mice. They inhibit convulsion in a H1-dependent fashion, while the neurons enhance it in a H3-receptor-mediated way.

The effects of diphenhydramine and SR142948A on periaqueductal gray neurons and on the interactions between the medial preoptic nucleus and the periaqueductal gray

The midbrain periaqueductal gray contains both neurotensin type-1 and type-2 receptors. Behavioral studies have shown that the analgesic effect of neurotensin is mediated through its interaction with the type-2 receptors. These receptors specifically bind the type-1 histamine antagonist, levocabastine. Recently, it has been shown that another histamine-1 antagonist, diphenhydramine, blocks the analgesic effect of neurotensin. In addition, it has been shown that a non-peptide neurotensin antagonist, SR142948A, binds to both types of neurotensin receptors and blocks the analgesic effect of exogenously applied neurotensin. Major afferents to the periaqueductal gray arise from the medial preoptic nucleus of the hypothalamus. This region contains neurotensinergic neurons, and the expression of neurotensin mRNA in this region increases following cold-water swim stress that leads to opioid-independent analgesia. The goal of this study was to determine whether the responses of periaqueductal gray neurons to stimulation of the medial preoptic nucleus are modified by local injection of diphenhydramine and SR142948A. Because the cellular basis of the effects of diphenhydramine on periaqueductal gray neurons had not been reported, we also examined the effects of diphenhydramine on the baseline-firing rate and synaptic transmission using in vivo and in vitro methods. The results of the in vitro studies indicate that diphenhydramine concentrations above 500 nM significantly reduce the baseline firing of the periaqueductal gray neurons without a significant effect on the frequency of postsynaptic potentials. At concentrations below 100 nM, diphenhydramine has little effect on the baseline-firing rate but partially blocks the response to neurotensin. The results of the in vivo studies showed similar effects of diphenhydramine. At high concentrations it inhibited periaqueductal gray neurons, but at low concentrations it had no effect on the baseline-firing rate and it blocked the response to neurotensin and to medial preoptic nucleus stimulation. Unlike diphenhydramine, SR142948A had virtually no effect on the baseline-firing rate but blocked the response to neurotensin and to stimulation of the medial preoptic nucleus. It is concluded that: (1) SR142948A, at a dose that completely blocks the effect of exogenously applied neurotensin on periaqueductal gray neurons, has little effect on their baseline-firing rates. (2) Because of its effect on the baseline-firing rate, only low doses of diphenhydramine can be used as an antagonist of the neurotensin analgesic effect. (3) Responses of periaqueductal gray neurons to medial preoptic nucleus stimulation is, in part, mediated by a neurotensinergic network within the periaqueductal gray.

Comparison of effects of lidocaine hydrochloride, buffered lidocaine, diphenhydramine, and normal saline after intradermal injection

Study Objective: To evaluate pain and the spread of analgesia when local anesthetics are given as an intradermal injection into the dorsal aspect of the hand. Design: Randomized, double-blinded, placebo-controlled study. Setting: University medical center. Patients: 40 consenting adult volunteers. Interventions: Volunteers were randomly assigned to receive a 0.25-mL injection of either lidocaine hydrochloride (1%), buffered lidocaine, diphenhydramine (1%), or placebo (0.9% sodium chloride solution) into the dorsal aspect of both hands. Measurements: The volunteers used a visual analog scale to compare the pain of needle insertion and solution injection. Then at 1, 2, 5, 10, 20, and 30 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed horizontally across the hand. Then at 32 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed vertically across the hand. The volunteers were called each day and asked the duration of their numbness or hyperesthesia until their hands were no longer numb or sore. Main Results : Buffered lidocaine during intradermal infiltration was found to be significantly (p < 0.05) less painful than either lidocaine hydrochloride or diphenhydramine and equivalent to placebo. Diphenhydramine and lidocaine hydrochloride during intradermal infiltration induced significantly (p < 0.05) more pain than buffered lidocaine or placebo. Lidocaine hydrochloride displayed a significantly (p < 0.05) larger diameter of analgesia than placebo by 1 minute after the injection, buffered lidocaine by 2 minutes after injection, and diphenhydramine by 5 minutes after injection. By 20 minutes after injection, diphenhydramine diameter of analgesia was significantly (p < 0.05) larger than placebo but significantly less than buffered lidocaine. By 30 minutes after injection, diphenhydramine diameter of analgesia was equivalent to placebo whereas buffered lidocaine and lidocaine diameters were still significantly (p < 0.05) larger than placebo. Diphenhydramine injection resulted in numbness that lasted significantly (p < 0.05) longer than other study solutions whereas buffered lidocaine and lidocaine injections resulted in numbness that lasted significantly longer than placebo. Diphenhydramine injection resulted in hyperesthesia that lasted for 2 or more days in 12 of the volunteers. Conclusion: There is a reduction of infiltration pain using buffered lidocaine as opposed to lidocaine and diphenhydramine. Although lidocaine injection resulted in a slightly faster spread of analgesic diameter, buffered lidocaine was equivalent to lidocaine from minute 2 until minute 30. Therefore, to obtain optimal anesthetic conditions, we recommend that buffered lidocaine be given 2 minutes before performing catheterization, whereas diphenhydramine should be given 5 minutes before catheterization, but only when buffered lidocaine cannot be used.